Identification of an Intronic Regulatory Element Necessary for Tissue-Specific Expression of in Thymic Epithelial Cells.

The thymus is critical for the establishment of the adaptive immune system and the development of a diverse T cell repertoire. T cell development depends upon cell-cell interactions with epithelial cells in the thymus. The thymus is composed of two different types of epithelial cells: cortical and medullary epithelial cells. Both of these express and critically depend on the transcription factor is also expressed in the hair follicle, and disruption of function in mice results in severe thymic developmental defects and the hairless (nude) phenotype. Despite its importance, little is known about the direct regulation of expression. In this study, we identify a -regulatory element (RE) critical for expression of in mouse thymic epithelial cells but dispensable for expression in hair follicles. Analysis of chromatin accessibility, histone modifications, and sequence conservation identified regions within the first intron of that possessed the characteristics of REs. Systematic knockout of candidate regions lead us to identify a 1.6 kb region that, when deleted, results in a near total disruption of thymus development. Interestingly, expression and function in the hair follicle were unaffected. RNA fluorescent in situ hybridization showed a near complete loss of mRNA expression in the embryonic thymic bud. Our studies have identified a genomic RE with thymic-specific control of gene expression.